Chronic pain originating from the musculo-skeletal system is a dominant cause of sick-leave in modern industry and can be very disabling and troublesome condition for the individual. The cause of this problem as it originates in muscle is unknown. However, one of the most frequent situations in which muscle pain is experienced is the cumulative trauma disorder (CTD) which results from repetitive movements especially common in assembly-line work. CTD is of special interest to NIOSH because these repeat motion injuries are one of the most difficult to anticipate and prevent. The aim of this proposal is to establish a rationale for the prevention of CTD by first understanding the etiology of the disorder and the tissue responses. Our studies in humans have shown that acute exposure to repetitive strain can lead to myofiber and fascial rupture without bleeding but still accompanied by muscle pain and restricted motion. Little is know about long-term response of muscles to repetitive mechanical loading where repeat injury occurs. To understand more thoroughly the responses of skeletal muscles to chronic injury, we have developed a rodent model of CTD. The objectives of the present study are: 1) to establish the functional outcome of chronic injury in rat leg muscles, 2) to characterize the nature of the inflammatory (acute or chronic), degenerative and regenerative responses and 3) to document changes in the extracellular matrix during the repair process which might lead to microfibrosis, restricted movement or impaired nutrient flow through the interstitial space. This research consists primarily of experiments in which muscles are chronically injured by mechanical overloading in deeply anesthetized rats. The tissues are surveyed at various time intervals by biochemical, immunohistochemical and histological techniques for specific cellular markers, components and mediators involved in cellular injury, inflammation and tissue repair. Intracellular and extracellular proteases, proteoglycans, collagens and other specific antigens have proven useful in observing the cellular and extracellular alterations. Insight into the mechanisms of muscle injury and repair following physiologic injury in rats subjected to CTD should provide a better understanding of the healing or failed-healing processes of muscle and the potential for tissue fibrosis and contracture as well as aid in the design of preventative regimens for individuals in specific industrial settings. The long range goal is to determine if movement dysfunction from cumulative trauma disorders (CTD) which injure muscles can be prevented by behavioral alteration without the need for job-site alterations.